{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T08:28:29Z","timestamp":1773304109431,"version":"3.50.1"},"reference-count":102,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2023,9,13]],"date-time":"2023-09-13T00:00:00Z","timestamp":1694563200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"GenomMed Horizon 2020 Framework Programme of the European Union","award":["740264"],"award-info":[{"award-number":["740264"]}]},{"name":"GenomMed Horizon 2020 Framework Programme of the European Union","award":["272249"],"award-info":[{"award-number":["272249"]}]},{"name":"GenomMed Horizon 2020 Framework Programme of the European Union","award":["338182"],"award-info":[{"award-number":["338182"]}]},{"name":"GenomMed Horizon 2020 Framework Programme of the European Union","award":["273909"],"award-info":[{"award-number":["273909"]}]},{"name":"GenomMed Horizon 2020 Framework Programme of the European Union","award":["317203"],"award-info":[{"award-number":["317203"]}]},{"name":"Medical Research Council of the Academy of Finland","award":["740264"],"award-info":[{"award-number":["740264"]}]},{"name":"Medical Research Council of the Academy of Finland","award":["272249"],"award-info":[{"award-number":["272249"]}]},{"name":"Medical Research Council of the Academy of Finland","award":["338182"],"award-info":[{"award-number":["338182"]}]},{"name":"Medical Research Council of the Academy of Finland","award":["273909"],"award-info":[{"award-number":["273909"]}]},{"name":"Medical Research Council of the Academy of Finland","award":["317203"],"award-info":[{"award-number":["317203"]}]},{"name":"Sigrid Juselius Foundation","award":["740264"],"award-info":[{"award-number":["740264"]}]},{"name":"Sigrid Juselius Foundation","award":["272249"],"award-info":[{"award-number":["272249"]}]},{"name":"Sigrid Juselius Foundation","award":["338182"],"award-info":[{"award-number":["338182"]}]},{"name":"Sigrid Juselius Foundation","award":["273909"],"award-info":[{"award-number":["273909"]}]},{"name":"Sigrid Juselius Foundation","award":["317203"],"award-info":[{"award-number":["317203"]}]},{"name":"Horizon 2020 Framework","award":["740264"],"award-info":[{"award-number":["740264"]}]},{"name":"Horizon 2020 Framework","award":["272249"],"award-info":[{"award-number":["272249"]}]},{"name":"Horizon 2020 Framework","award":["338182"],"award-info":[{"award-number":["338182"]}]},{"name":"Horizon 2020 Framework","award":["273909"],"award-info":[{"award-number":["273909"]}]},{"name":"Horizon 2020 Framework","award":["317203"],"award-info":[{"award-number":["317203"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>We tested a hypothesis that in silico-discovered compounds targeting traumatic brain injury (TBI)-induced transcriptomics dysregulations will mitigate TBI-induced molecular pathology and augment the effect of co-administered antiseizure treatment, thereby alleviating functional impairment. In silico bioinformatic analysis revealed five compounds substantially affecting TBI-induced transcriptomics regulation, including calpain inhibitor, chlorpromazine, geldanamycin, tranylcypromine, and trichostatin A (TSA). In vitro exposure of neuronal-BV2-microglial co-cultures to compounds revealed that TSA had the best overall neuroprotective, antioxidative, and anti-inflammatory effects. In vivo assessment in a rat TBI model revealed that TSA as a monotherapy (1 mg\/kg\/d) or in combination with the antiseizure drug levetiracetam (LEV 150 mg\/kg\/d) mildly mitigated the increase in plasma levels of the neurofilament subunit pNF-H and cortical lesion area. The percentage of rats with seizures during 0\u201372 h post-injury was reduced in the following order: TBI-vehicle 80%, TBI-TSA (1 mg\/kg) 86%, TBI-LEV (54 mg\/kg) 50%, TBI-LEV (150 mg\/kg) 40% (p &lt; 0.05 vs. TBI-vehicle), and TBI-LEV (150 mg\/kg) combined with TSA (1 mg\/kg) 30% (p &lt; 0.05). Cumulative seizure duration was reduced in the following order: TBI-vehicle 727 \u00b1 688 s, TBI-TSA 898 \u00b1 937 s, TBI-LEV (54 mg\/kg) 358 \u00b1 715 s, TBI-LEV (150 mg\/kg) 42 \u00b1 64 (p &lt; 0.05 vs. TBI-vehicle), and TBI-LEV (150 mg\/kg) combined with TSA (1 mg\/kg) 109 \u00b1 282 s (p &lt; 0.05). This first preclinical intervention study on post-TBI acute seizures shows that a combination therapy with the tissue recovery enhancer TSA and LEV was safe but exhibited no clear benefit over LEV monotherapy on antiseizure efficacy. A longer follow-up is needed to confirm the possible beneficial effects of LEV monotherapy and combination therapy with TSA on chronic post-TBI structural and functional outcomes, including epileptogenesis.<\/jats:p>","DOI":"10.3390\/ijms241814049","type":"journal-article","created":{"date-parts":[[2023,9,14]],"date-time":"2023-09-14T09:57:56Z","timestamp":1694685476000},"page":"14049","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Treatment of Status Epilepticus after Traumatic Brain Injury Using an Antiseizure Drug Combined with a Tissue Recovery Enhancer Revealed by Systems Biology"],"prefix":"10.3390","volume":"24","author":[{"given":"Natallie","family":"Kajevu","sequence":"first","affiliation":[{"name":"A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, P.O. Box 1627, 70211 Kuopio, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4403-9084","authenticated-orcid":false,"given":"Anssi","family":"Lipponen","sequence":"additional","affiliation":[{"name":"A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, P.O. Box 1627, 70211 Kuopio, Finland"},{"name":"Expert Microbiology Unit, Finnish Institute for Health and Welfare, P.O. Box 95, 70701 Kuopio, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9118-8341","authenticated-orcid":false,"given":"Pedro","family":"Andrade","sequence":"additional","affiliation":[{"name":"A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, P.O. Box 1627, 70211 Kuopio, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ivette","family":"Ba\u00f1uelos","sequence":"additional","affiliation":[{"name":"A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, P.O. Box 1627, 70211 Kuopio, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Noora","family":"Puhakka","sequence":"additional","affiliation":[{"name":"A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, P.O. Box 1627, 70211 Kuopio, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elina","family":"H\u00e4m\u00e4l\u00e4inen","sequence":"additional","affiliation":[{"name":"A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, P.O. Box 1627, 70211 Kuopio, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Teemu","family":"Natunen","sequence":"additional","affiliation":[{"name":"Institute of Biomedicine, University of Eastern Finland, P.O. Box 1627, 70211 Kuopio, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3566-4096","authenticated-orcid":false,"given":"Mikko","family":"Hiltunen","sequence":"additional","affiliation":[{"name":"Institute of Biomedicine, University of Eastern Finland, P.O. Box 1627, 70211 Kuopio, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8163-5416","authenticated-orcid":false,"given":"Asla","family":"Pitk\u00e4nen","sequence":"additional","affiliation":[{"name":"A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, P.O. Box 1627, 70211 Kuopio, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1637","DOI":"10.1016\/j.apmr.2010.05.017","article-title":"Position Statement: Definition of Traumatic Brain Injury","volume":"91","author":"Menon","year":"2010","journal-title":"Arch. Phys. Med. Rehabil."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1097\/01.HTR.0000314531.30401.39","article-title":"Incidence of Long-Term Disability Following Traumatic Brain Injury Hospitalization, United States, 2003","volume":"23","author":"Selassie","year":"2008","journal-title":"J. Head Trauma Rehabil."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1097\/HTR.0b013e3181ccc8b4","article-title":"The Epidemiology of Traumatic Brain Injury","volume":"25","author":"Selassie","year":"2010","journal-title":"J. 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